Response to Comments: Oxygen and Oxygen Equipment - DL33797

One clinical association requested a change in language in DL33797 from “treating physician” to “treating practitioner.”

The final LCD is reflective of this request.

Several commenters, including one clinical association wondered about the composition (lack of a podiatrist on the panel) and overall capabilities of the Contract Advisory Committee (CAC).

All relevant stakeholders, and clinical organizations/associations were invited to nominate candidates for the CAC, and the majority chose not to do so.

The CAC panel was comprised of distinguished clinicians and investigators with extensive experience in critically reviewing the clinical literature.

Several commenters, including two authors of publications listed in the bibliography (one of whom also wrote a second letter on behalf of a clinical association) felt that several of the Randomized Controlled Trials (RCTs) listed in the bibliography met all the elements in strength and design that CMS required of a “gold standard” study.

CMS has made note of study design and methodological attributes that are usually associated with stronger, higher quality evidence; however, study design is but one input when assessing how much weight to assign to the results of a trial. Even a well-designed RCT might still have other weaknesses that lower the overall strength of the evidence.

For example, the sample size (n) of an RCT is an important variable, since the variation of the mean is inversely proportional to the sample size. In other words, when the n is low, there is an increased likelihood that another trial of the same size (or larger) by the same investigators may yield different results. Thus, the weight attributed to an RCT may be lower than expected due to the number of subjects in the active arm of the study, particularly if insufficiently powered.

Baseline patient heterogeneity between arms that may affect wound healing, standards of wound care, statistical tools used for analysis of the results, and applicability to the Medicare population are some of the other inputs that are also considered when weighing the results of a study.

Of note, applicability to the Medicare population is not only an age criterion, but also reflective of the typical co-morbidities of Medicare beneficiaries, which would have excluded them from participating in some of the trials due to the exclusion criteria(s).

Section 13.2.3 of Chapter 13 of the Program Integrity Manual notes: “Acceptance by individual health care providers, or even a limited group of health care providers, does not indicate general acceptance of the item or service by the medical community.”

Thus, well-designed RCTs inform, but by themselves are not reflective of general acceptance by the medical community.

Several commenters felt that the DME MACs should have independently evaluated the different modalities of oxygen delivery, and their effects on different types of wounds. Two broad subcategories to this group of comments are noted below.

1. Each mode of oxygen delivery was championed by individual commenters who thought that their favored modality was superior to the others in terms of wound healing or quality of life measures and thus, should be selected for separate coverage.
2. Several commenters also felt that specific wound types (for example diabetic foot ulcers) should be covered, instead of a blanket not reasonable and necessary determination.

As noted by one commenter, National Coverage Determinations (NCDs) and LCDs routinely consider specific subtypes of populations and/or conditions for coverage when applicable. The DME MACs did independently consider the different modes of oxygen delivery and wound types during the drafting of DL33797.

The rationale in DL33797 includes an independent assessment of recent studies that utilized different modes of oxygen delivery, and that assessment was further categorized by wound types. Although all the studies in the bibliography were not summarized in the rationale due to space limitations, all were independently evaluated. Thus, the final policy determination is reflective of the independent assessments of the entire body of literature noted in the bibliography.

Our response to comment # 3 above is reflective of an independent assessment of recent RCTs involving diabetic foot ulcers, and the subsequent policy determinations regarding coverage.

Several commenters felt that the external assessments did not include the latest publications, and furthermore were not available to the general public.

Several commenters also felt that the evidence analysis was incomplete and thus inaccurate because the DME MACs did not consider all of the latest publications, such as the Frykberg RCT.

The distribution of external assessments is contractually bounded. All external assessments are available for purchase at www.ecri.org. However, we would like to note that the external assessments utilized the same peer-reviewed literature included in the bibliography of DL33797, and thus, the source materials are all publicly available.

The DME MACs do not rely solely on external assessments during the policy making process. External assessments are but one input – they inform but are not dispositive in the policy making process.

The DME MACs and the CAC independently reviewed the peer-reviewed publications, including the Frykberg RCT on diabetic foot ulcers, which is the first publication listed in the bibliography of DL33797.

Finally, as noted in our response to comment #3 above, RCTs inform, but by themselves are not reflective of general acceptance by the medical community.

Several commenters discussed their personal experiences with Topical Oxygen Treatment (TOT) used for the treatment of non-healing wounds.

The DME MAC Medical Directors would like to thank patients, Medicare beneficiaries, and practitioners for sharing their stories and clinical experiences.

However, when determining if a treatment is “reasonable and necessary” for purposes of Medicare reimbursement, CMS instructs the DME MACs to rely on published peer-reviewed clinical literature, clinical guidelines, consensus documents, etc. (see CMS Program Integrity Manual (PIM), Chapter 13).

Several commenters suggested that the CAC meeting did not adhere to the instructions in Chapter 13 of the PIM.

The CAC meeting met all the required elements noted in Chapter 13, Section 13.2.4.3 of the PIM.

Several commenters thought that the CAC focused on a “flawed” 2017 CMS Decision Memo and did not adequately discuss some of the more recent publications listed in the bibliography.

The DME MACs neither dictate nor control what CAC members may choose to focus on in their deliberations.

The CAC deliberations were informed by the Key Questions, and all CAC members received the clinical literature referenced in DL33797, which included the latest publications.

Several commenters disagreed with the assessment of the level of evidence.

Policies are usually grounded on a body of literature. Thus, although certain studies were independently rated as “moderate”, the overall quality of the body of evidence was low, since the overall assessment was derived from the peer-reviewed publications listed in the bibliography.

Several commenters thought that the DME MACs focused on a “flawed” 2017 CMS Decision Memo and did not adequately discuss some of the more recent publications listed in the bibliography.

While DL33797 does refer to the 2017 CMS Decision Memo, the DME MACs performed an independent assessment of the clinical evidence, including studies that appeared subsequent to the publication of the CMS Memo, as required by Chapter 13 of the PIM.

Several commenters thought that substantial real-world clinical evidence, some published in retrospective studies, and other observational studies demonstrated that topical oxygen was efficacious in the treatment of chronic wounds.

As noted in several recent editorials in the New England Journal of Medicine and the British Medical Journal, all evidence, including RCTs is “real-world” evidence.

Retrospective and observational non-randomized studies may be useful, but are generally regarded to be of lower quality, because the lack of randomization does not allow for the control of “known” and “unknown” biases.

Thus, when available, prospective RCTs are generally acknowledged to offer higher quality evidence.

Several commenters indicated that the products should be covered since they are FDA-approved.

FDA approval is a necessary but insufficient condition for the determination that an item is “reasonable and necessary” for purposes of Medicare reimbursement.

Several commenters noted that topical oxygen is covered by the VA, some State Medicaid programs, and by some private insurers - and thus, should also be covered by Medicare.

Coverage determinations by commercial payers and other non-Medicare entities are informative, but not dispositive, for the purposes of Medicare determinations of what is “reasonable and necessary.”

Several commenters indicated that in their clinical experience, TOT was superior and cost-effective when compared to Hyperbaric Oxygen Therapy (HBOT) for the treatment of diabetic foot ulcers.

The DME MACs thank the wound care providers for sharing their experience with HBOT versus TOT in their clinical practices. However, the commenters did not submit any peer-reviewed clinical literature to support these observations.

Several commenters indicated that the several of the peer-reviewed publications should not have been included in the analysis.

Policies are usually grounded on a body of literature. The overall assessment was derived from the peer-reviewed publications listed in the bibliography.

Several commenters requested a delay in finalizing DL33797 noting that a large-scale (>100 enrollees, with >50% Medicare-age), multicenter, prospective randomized controlled trial (“RCT”) evaluating the use of a new TOT system in treating diabetic wounds is well underway and is expected to be completed and published within this LCD reconsideration timeline.

Chapter 13 of the PIM enumerates the LCD reconsideration request timelines. Thus, the DME MACs do not have the discretion to change those timelines.

Unlike the FDA approval process where one pivotal study may result in approval of a drug or device, the DME MACs consider a broader body of evidence and general acceptance during the policy making process.

Several commenters noted the Driver et al. studies should not be included in the analysis as the technology investigated in those trials was disposable and did not meet the definition of DME.

The DME MACs thank the commenters for pointing out that the device used in these studies was disposable. However, the DME MACs review of the literature, including the CAC Key Questions, was geared towards an evidentiary assessment of the effectiveness and general acceptance of topical oxygen for the treatment of chronic wounds. Thus, the publications by Driver et. al. were germane to our assessment.

Several commenters felt that some clinical guideline recommendations may have been influenced by potential financial conflicts of interest.

The DME MACs rely on the clinical organizations to monitor and mitigate the risk of conflicts of interest with their guidelines.

The DME MACs note that clinical guidelines are but one input – they inform but are not dispositive in the policy making process.

Several commenters questioned why studies from Bowen et. al. and Lavery et. al. were not referenced in the proposed LCD.

The 2019 publication by Lavery et. al. is included in the bibliography and was considered.

The publication by Bowen et. al. was not published in a peer-reviewed journal as required in Chapter 13, Section 13.5.3 of the PIM, and was thus not considered.

Several commenters questioned if NPWT or HBO would be a covered benefit if given the same level of scrutiny as TOT.

A comparative evidentiary assessment of other NCDs and LCDs is outside the scope of this reconsideration request.

Several commenters indicated the draft LCD does not accurately incorporate the outcomes from the most recent AOTI RCT in DFUs that was published in Diabetes Care on 10/16/19 after the reconsideration process had commenced.

Please see our response to comments # 3, 4 and 5 above. The DME MAC Medical Directors fully analyzed all outcomes published in the AOTI RCT in DFUs.

One commenter was concerned that the CAC process for TOT was conducted very differently than the Tumor Treatment Field Therapy (TTFT) CAC process (DL34823). They Specifically noted concerns included member selection, manufacturer involvement, the length of meeting, and location.

As noted in our response to comment #7 above, the CAC meeting met all the required elements noted in Section 13.2.4.3 of Chapter 13 of the Program Integrity Manual (PIM).

The PIM is not proscriptive regarding any of the concerns expressed by the commenter.

Several commenters noted that TOT is safer than other wound treatment therapies, such as NPWT.

Safety is the purview of the Food and Drug Administration, and the DME MACs only review items that have received FDA approval.